title: Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death.
abstract: Neuronal apoptotic death generally requires de novo transcription, and activation of the transcription factor c-Jun has been shown to be necessary in multiple neuronal death paradigms. Caspase-2 has been implicated in death of neuronal and non-neuronal cells, but its relationship to transcriptional activation has not been clearly elucidated. In the present study, using two different neuronal apoptotic paradigms, β-amyloid treatment and NGF (nerve growth factor) withdrawal, we examined the hierarchical role of caspase-2 activation in the transcriptional control of neuron death. Both paradigms induce rapid activation of caspase-2 as well as activation of the transcription factor c-Jun and subsequent induction of the pro-apoptotic BH3 (Bcl-homology domain 3)-only protein Bim (Bcl-2-interacting mediator of cell death). Caspase-2 activation is dependent on the adaptor protein RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, and both caspase-2 and RAIDD are required for c-Jun activation and Bim induction. The present study thus shows that rapid caspase-2 activation is essential for c-Jun activation and Bim induction in neurons subjected to apoptotic stimuli. This places caspase-2 at an apical position in the apoptotic cascade and demonstrates for the first time that caspase-2 can regulate transcription.
authors.affiliation: *Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, U.S.A.
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Jean
authors.forename: Elena M
authors.initials: EM
authors.lastname: Ribe
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Pero
authors.forename: Marina
authors.initials: M
authors.lastname: Moskalenko
authors.forename: Zarah
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Lianna J
authors.initials: LJ
authors.lastname: Marks
authors.forename: Lloyd A
authors.initials: LA
authors.lastname: Greene
authors.forename: Carol M
authors.initials: CM
authors.lastname: Troy
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053420:CRADD Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D053143:Caspase 2 / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000172:deficiency; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D053420:CRADD Signaling Adaptor Protein; C495182:Cradd protein, rat; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D020932:Nerve Growth Factor; D053143:Caspase 2